O'Brien S F, McKendrick J D, Radomski M W, Davidge S T, Russell J C
Department of Surgery, University of Alberta, Edmonton, Canada.
Can J Physiol Pharmacol. 1998 Jan;76(1):72-6.
Insulin resistance is associated with an increased risk of cardiovascular disease that is probably related to abnormalities of vascular wall function. The JCR:LA-cp rat is a unique animal model of human vascular disease that exhibits a profound insulin resistance, vasculopathy, and cardiovascular disease, and allows study of the relationships between insulin resistance and vascular function. Conductance and resistance arteries serve different functions, thus vascular disease may affect these types of artery differently. Concentration-response curves to norepinephrine, phenylephrine, and acetylcholine were studied in conductance vessels (aortic rings) and resistance vessels (mesenteric arteries) from 12-week-old male obese and lean JCR:LA-cp rats. The aortic rings and mesenteric arteries from obese rats showed increased maximal response to phenylephrine compared with those from lean rats, whereas only the mesenteric arteries from obese rats showed increased maximal response to norepinephrine. In aortic rings, relaxation to acetylcholine was similar for both genotypes, but the mesenteric arteries of obese rats showed impaired relaxation to acetylcholine. We conclude that the sensitivity to vasoconstriction is enhanced in aortic rings and mesenteric arteries of obese male JCR:LA-cp rats, but endothelial function is impaired only in the mesenteric resistance arteries of these animals. Hence functional aberrations in the obese, insulin-resistant state are more pronounced in mesenteric resistance arteries than in a major conductance artery.
胰岛素抵抗与心血管疾病风险增加相关，这可能与血管壁功能异常有关。JCR:LA-cp大鼠是一种独特的人类血管疾病动物模型，表现出严重的胰岛素抵抗、血管病变和心血管疾病，可用于研究胰岛素抵抗与血管功能之间的关系。传导动脉和阻力动脉发挥不同的功能，因此血管疾病可能对这些类型的动脉产生不同影响。研究了12周龄雄性肥胖和瘦JCR:LA-cp大鼠的传导血管（主动脉环）和阻力血管（肠系膜动脉）对去甲肾上腺素、苯肾上腺素和乙酰胆碱的浓度-反应曲线。与瘦大鼠相比，肥胖大鼠的主动脉环和肠系膜动脉对苯肾上腺素的最大反应增加，而只有肥胖大鼠的肠系膜动脉对去甲肾上腺素的最大反应增加。在主动脉环中，两种基因型对乙酰胆碱的舒张反应相似，但肥胖大鼠的肠系膜动脉对乙酰胆碱的舒张反应受损。我们得出结论，肥胖雄性JCR:LA-cp大鼠的主动脉环和肠系膜动脉对血管收缩的敏感性增强，但仅这些动物的肠系膜阻力动脉的内皮功能受损。因此，肥胖、胰岛素抵抗状态下的功能异常在肠系膜阻力动脉中比在主要传导动脉中更明显。
